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X. To compare the effect of XRT in patients receiving mastectomy and in patients receiving lumpectomy.

XI. To examine the role of proliferation measures as a prognosticator for patients with residual disease after neoadjuvant chemotherapy.

XII. To develop predictors of the degree of reduction in local regional recurrence (LRR).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM 1: Patients are assigned to 1 of 2 treatment groups.

GROUP 1A: Lumpectomy patients undergo whole breast radiation therapy using IMRT or 3DCRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.

GROUP 1B: Mastectomy patients do not undergo radiation therapy.

ARM 2: Patients are assigned to 1 of 2 treatment groups.

GROUP 2A: Lumpectomy patients undergo regional nodal radiation therapy with whole breast radiation therapy using IMRT or 3DCRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.

GROUP 2B: Mastectomy patients undergo regional nodal radiation therapy and chestwall XRT using IMRT or 3DCRT once daily 5 days a week for 5 weeks.

All patients also receive systemic therapy as planned (hormonal therapy for patients with hormone-receptor positive breast cancer and trastuzumab or other anti-human epidermal growth factor receptor 2 [HER2] therapy for patients with breast cancer that is HER2-positive).

After completion of study treatment, patients are followed up at 6, 12, 18, and 24 months and then yearly for 8 years.

Lumpectomy patients undergo whole breast radiation therapy using IMRT or 3D-CRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.

Radiation: WBI

Other Name: Whole Breast Irradiation (WBI)

No Intervention: Group 1B Mastectomy: No regional nodal or chestwall XRT

Mastectomy patients do not undergo radiation therapy.

Experimental: Group 2A lumpectomy: Regional nodal XRT with WBI

Lumpectomy patients undergo regional nodal radiation therapy with whole breast radiation therapy using IMRT or 3D-CRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.

IBC-RFI [ Time Frame: Time from randomization until invasive local, regional, or distant recurrence, or death from breast cancer, assessed up to 10 years ]

Secondary Outcome Measures :

OS [ Time Frame: Time from randomization to death from any cause, assessed up to 10 years ]

LRRFI [ Time Frame: Time from randomization to recurrence of primary cancer w/in breast or lymph nodes in ipsilateral axilla, infraclavicular fossa, or ipsilateral internal mammary chain w/out evidence distant disease, or death due to breast cancer, assessed up to 10 years ]

DRFI [ Time Frame: Time from randomization to the development of tumor in all areas beyond local or regional limits, or death due to breast cancer, assessed up to 10 years ]

DFS-DCIS [ Time Frame: Time from randomization to local recurrence post-mastectomy/in ipsilateral breast post-lumpectomy, regional/distant recurrence, contralateral disease, second primary cancer, or death from any cause prior to recurrence or SPC, assessed up to 10 years ]

Time to SPC [ Time Frame: Time from randomization to the development of a second primary invasive cancer of any site excluding squamous and basal cell carcinoma of the skin, assessed up to 10 years ]

Effect of radiation therapy on cosmetic outcome in mastectomy and lumpectomy patients as assessed by quality of life questionnaire [ Time Frame: Assessed prior to randomization, 3 months or at end of RT, and 6, 12, and 24 months from randomization ]

Frequencies of adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ]

Molecular predictors of recurrence [ Time Frame: Tissue samples collected within 90 days after randomization ]

To test the prognostic role of gene expression profiles in residual tumor tissue and to develop predictors of the degree of reduction of loco-regional recurrence.

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Layout table for eligibility information

Ages Eligible for Study:

18 Years and older (Adult, Older Adult)

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines

The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Patient must have had pathologic confirmation of axillary nodal involvement at presentation (before neoadjuvant therapy) based on either a positive fine needle aspirate (FNA) (demonstrating malignant cells) or positive core needle biopsy (demonstrating invasive adenocarcinoma); the FNA or core needle biopsy can be performed either by palpation or by image guidance; documentation of axillary nodal positivity by sentinel node biopsy (before neoadjuvant therapy) is not permitted

Patients must have had estrogen receptor (ER) analysis performed on the primary breast tumor before neoadjuvant therapy according to current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing; if negative for ER, assessment of progesterone receptor (PgR) must also be performed according to current ASCO/CAP guideline recommendations for hormone receptor testing (http://www.asco.org)

Patients must have had HER2 testing performed on the primary breast tumor before neoadjuvant chemotherapy according to the current ASCO/CAP guideline recommendations for human epidermal growth factor receptor 2 testing in Breast Cancer (http://www.asco.org); patients who have a primary tumor that is either HER2-positive or HER2-negative are eligible

Patient must have completed a minimum of 8 weeks of standard neoadjuvant chemotherapy consisting of an anthracycline and/or taxane-based regimen

For patients who receive adjuvant chemotherapy after surgery, a maximum of 12 weeks of intended chemotherapy may be administered but must be completed before randomization; (if treatment delays occur, chemotherapy must be completed within 14 weeks); the dose and schedule of the adjuvant chemotherapy are at the investigator's discretion; Note: It is preferred that all intended chemotherapy be administered in the neoadjuvant setting

Patients with HER2-positive tumors must have received neoadjuvant anti-HER2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen), unless medically contraindicated

At the time of definitive surgery, all removed axillary nodes must be histologically free from cancer; acceptable procedures for assessment of axillary nodal status at the time of surgery include:

Axillary node dissection

Sentinel node biopsy alone or

Sentinel node biopsy followed by axillary node dissection

Note: Patients are eligible whether there is residual invasive carcinoma in the surgical breast specimen or whether there is evidence of pathologic complete response; patients who are found to be pathologically node-positive at the time of surgery, based on sentinel node biopsy alone, are candidates for A011202, a study developed by the Alliance in Oncology, an NCI Cooperative Group; if A011202 is open at the investigator's institution, patients should be approached about participating in the A011202 study

Patients with pathologic staging of ypN0(i+) or ypN0(mol+) are eligible (Note: Postneoadjuvant therapy is designated with a "yp" prefix.)

Patient who have undergone either a total mastectomy or a lumpectomy are eligible

For patients who undergo lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS as determined by the local pathologist; additional operative procedures may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible; (patients with margins positive for lobular carcinoma in situ [LCIS] are eligible without additional resection)

For patients who undergo mastectomy, the margins must be histologically free of residual (microscopic or gross) tumor

The interval between the last surgery for breast cancer (including re-excision of margins) and randomization must be no more than 70 days; also, if adjuvant chemotherapy was administered, the interval between the last chemotherapy treatment and randomization must be no more than 70 days

The patient must have recovered from surgery with the incision completely healed and no signs of infection

If adjuvant chemotherapy was administered, chemotherapy-related toxicity that may interfere with delivery of radiation therapy should have resolved

Any prior history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated with radiation therapy; (patients with synchronous or previous ipsilateral LCIS are eligible)

History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization

Any radiation therapy for the currently diagnosed breast cancer prior to randomization

Any continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy; patients are eligible if these medications are discontinued prior to randomization

Pregnancy or lactation at the time of study entry; (Note: Pregnancy testing must be performed within 2 weeks prior to randomization according to institutional standards for women of childbearing potential)

Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up

Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements